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Faithful chromosome segregation during mitosis requires the correct assembly of kinetochore on the centromere. CENP-A is a variant of histone H3, which specializes the centromere region on chromatin and mediates the kinetochore assembly. The Mis18 complex plays a critical role in initiating the centromere loading of the newly-synthesized CENP-A. However, it remains unclear how Mis18 complex (spMis18, spMis16 and spMis19) is located to the centromere to license the recruitment of Cnp1CENP-A in Schizosaccharomyces pombe. We found that spMis18 directly binds to nucleosomal DNA through its extreme C-terminus and interacts with H2A-H2B dimer via the acidic region on the surface of its Yippee-like domain. Live-cell imaging confirmed that mutation of the acidic region and deletion of the extreme C-terminus significantly impairs the localization of spMis18 and Cnp1 to the centromere and delays chromosome segregation during mitosis. Our findings illustrate that the interaction of spMis18 with histone H2A-H2B and DNA plays important roles in the recruitment of spMis18 and Cnp1 to the centromere in fission yeast.

Citation

Min Zhang, Fan Zheng, Yujie Xiong, Chen Shao, Chengliang Wang, Minhao Wu, Xiaojia Niu, Fenfen Dong, Xuan Zhang, Chuanhai Fu, Jianye Zang. Centromere targeting of Mis18 requires the interaction with DNA and H2A-H2B in fission yeast. Cellular and molecular life sciences : CMLS. 2021 Jan;78(1):373-384

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PMID: 32318758

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